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Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein

Abstract:

The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which contains a docking site for substrates called the PIF pocket. Here, we used a chemical biology approach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities. The inositol polyphosphate derivative HYG8 ...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/scisignal.add3184

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Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
ORCID:
0000-0001-9003-3540
Publisher:
American Association for the Advancement of Science
Journal:
Science Signaling More from this journal
Volume:
16
Issue:
789
Article number:
eadd3184
Publication date:
2023-06-13
Acceptance date:
2023-05-19
DOI:
EISSN:
1937-9145
ISSN:
1945-0877
Language:
English
Keywords:
Pubs id:
1392454
Local pid:
pubs:1392454
Deposit date:
2023-06-12

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